Contamination of conventional eukaryotic cell culture media with “adventitious particles” such as bacterial, virus or prion particles is a serious potential problem in the industrial preparation of biopharmaceuticals such as antibodies or therapeutic proteins. Such contaminants in a biopharmaceutical are capable of causing patient infections and disease and may limit yields due to increased metabolic burdens on the host productioncell line.
Variant Creutzfeldt-Jakob disease (vCJD) is one example of a patient disease that could be caused by adventitious particle contamination. This disease is prion mediated in humans and is characterized by fatal neurodegeneration. vCJD has been strongly linked with exposure to the Bovine Spongiform Encephalopathy (BSE) prion which causes fatal, neurodegenerative “Mad Cow Disease” in cattle.
Adventitious particle contamination of conventional eukaryotic cell culture media can result from the incorporation of animal-derived components and protein growth factors into conventional media. Such contamination can occur when animal-derived media components are harvested from an animal harboring disease-causing bacteria, viruses, or prions. For example, bovine serum harvested from a cow with BSE may be contaminated with prions capable of causing human vCJD. The ultimate result of such adventitious particle contamination can be the contamination of eukaryotic cell cultures and the biopharmaceuticals prepared from such cultures.
Adventitious particle contamination can be avoided by culturing eukaryotic cells in animal component free cell culture media. Ideally, such media are “chemically defined” such that the media compositions contain only known chemical compounds, and are free of all proteins—even those not of animal origin such as recombinant proteins.
Chemically defined media compositions optimal for production of biopharmaceuticals, such as antibodies, must satisfy several different criteria. First, such compositions must limit eukaryotic cell damage resulting from shear forces and other cell-damaging processes that occur in the bioreactor vessels typically used for biopharmaceutical production. Second, such compositions must enable eukaryotic cell cultures to have high viable cell densities (i.e., number viable cells/ml media) and high percentages of viable cells. Third, such compositions must permit high titers of secreted biopharmaceutical products (i.e., antibody mg/L media) and high specific productivities (i.e., pg antibody/viable cell/day). Lastly, such compositions must limit the production of lactic acid by cultured eukaryotic cells to permit the most efficient cellular use of glucose.
Thus, a need exists for chemically defined media compositions which satisfy these criteria and are optimized for biopharmaceutical production.